Glucocorticoids influence performance on declarative memory tasks and tasks of memory for emotional information. The cognitive effects of exogenous glucocorticoids depend on dose, the time period between administration and testing, and the time of testing within the diurnal pattern of cortisol secretion. Additionally, glucocorticoid administration can influence mood, and with chronic administration glucocorticoids may lead to the development of mania or depression. A potential mechanism by which glucocorticoids may influence emotional behavior is via their effects on the neurophysiological activity of the amygdala and prefrontal cortical structures known to participate in emotional processing. Human imaging studies indicate that the amygdala, ventral medial prefrontal, and other prefrontal cortical areas are activated during tasks requiring processing of affective stimuli. These data converge with lesion analysis and electrophysiological studies performed in humans or experimental animals to indicate that these structures participate in brain circuits that process emotional information. These brain structures contain dense concentrations of glucocorticoid mRNA and receptors. Increased glucocorticoids appear to potentiate activation of the amygdala and affect processing of emotionally laden stimuli based on both experimental animal studies and correlational human studies. The present study investigates the influence of glucocorticoids on the hemodynamic response that occurs while processing emotionally-valenced visual stimuli known to activate the amygdala and anatomically-related areas of the prefrontal cortex (PFC) in healthy humans. Functional magnetic resonance images will be acquired during the performance of tasks that involve viewing emotionally expressive faces both before and following either hydrocortisone (synthetic cortisol) (0.15 mg/kg or 0.45 mg/kg bolus) or placebo administration. The change in the BOLD signal in structures of interest will be compared across high dose cortisol, low dose cortisol and placebo conditions. In addition, the effects of hydrocortisone on relative blood flow in the amygdala and PFC will be assessed using an arterial spin labeling (ASL) technique to measure perfusion. The findings of this study will guide future research into the effects of glucocorticoids on emotional perception in subjects with mood disorders. During the past one year 12 subjects have been entered into the study and successfully scanned under both placebo and hydrocortisone conditions. The image data have been analyzed and show that hydrocortisone administration potentiated the amygala, inferotemporal and lateral orbital cortex responses to fearful and sad faces. We also demonstrated differential effects between high and low dose hydrocortisone administration in the amygdala and anterior cingulate, areas that play major roles in emotional behavior and memory. These findings provide important insights as to the mechanisms via which cortisol release may facilitate responses to stressors or threats, and show the differences between these responses during exposure to the amount of cortisol released during mild versus severe stress (i.e., low and high dose hydrocortisone, respectively). During the upcoming one year, a depressed group will be added to investigate whether differential responsiveness to glucocorticoid receptor stimulation exists in depression.